Biocompatible material and device

ABSTRACT

A biodegradable composite material or device including at least one biodegradable polymer matrix material and at least one filler component. The material or device has an initial shape and at least one evolved shape. The evolved shape is different from the initial shape. The initial shape is adapted to change towards the evolved shape. The filler component is adapted to accelerate and/or amplify the transformation from the initial shape towards the evolved shape when the external stimulus for transformation is given by physiological conditions. Also a method to control the shape transformation rate of a composite material or device.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is the national phase under 35 U.S.C. §371 ofPCT/FI2010/050384 filed 11 May 2010.

FIELD OF THE INVENTION

The present invention relates to biocompatible, biodegradable materialsand devices, especially to composite materials and devices that arefabricated of biodegradable polymers, copolymers or polymer blends andthat contain filler component. The invention also relates to a method tocontrol shape transformation of biodegradable polymer composite materialor device in physiological conditions.

BACKGROUND

Shape-memory effect has been described for different material classes:polymers, metals and ceramics. First materials with shape-memory weremetallic alloys. Shape-memory materials are stimuli-responsive materialsand are used in different fields of industry, e.g in aircraft, piping,textiles, packaging, optometry and in medicine e.g. in orthopedics andminimally invasive surgery. Over shape-memory metallic alloys andceramics, shape memory polymers have, for example, the advantage oflight weight, low cost, good processability, high shape deformabilityand shape recoverability.

Shape-memory polymers are a class of smart and functional polymers.Shape-memory polymeric material may be biodegradable ornon-biodegradable. Combination of shape-memory capability,biocompatibility, biodegradability and tailored mechanical propertiescan be mentioned to highlight the versatility of shape-memory polymersas biomaterials and their applicability in medical devices.

Shape-memory is a material property where the deformed polymericmaterial has an ability to return from a deformed, temporary shape,towards the original, permanent shape. Shape-memory polymers andproducts made of them can change their shapes from a temporary shape totheir original shapes under appropriate activation or external stimulussuch as e.g. temperature, light, pH, solvent composition, specific ionsor enzymes. A change in shape induced by a change in temperature iscalled thermally induced shape memory effect.

Conventional shape-memory effect results from the polymer's structurelike a multiblock copolymer structure. Shape memory polymers generallycontain two separate phases (like different components on molecularlevel): a fixing phase and a reversible phase. Fixing phase may containphysical or chemical cross-linking molecular structure (cross-linkedpolymer network) or crystalline phase and reversible phase may beamorphous.

Shape-memory polymers have potential applications also in medicaldevices. If the medical device is not intended to be permanent it ispossible to use biodegradable polymer(s). Promising fields are minimallyinvasive surgery and also scaffolding and suturing devices for assistingin tissue repair. Following publications describe the aforementioned andother applications and devices, e.g. Lendlein and Langer, Science 296(2002) 1673-6, U.S. Pat. No. 6,281,261, EPO Pat no. 1,056,487.

One limit of prior art biodegradable shape-memory polymers is thatshape-memory effect is typically thermally induced, which usually meanstemperatures above polymer glass transition temperature, T_(g),typically temperatures between 45° to 70° C. Another disadvantage ofprior art shape-memory polymers, is their low mechanical strength.

In order to improve the material properties or obtain new functions ofshape-memory polymers, shape-memory composites and blends can beprepared, as described in Zheng et al., Biomaterials 27 (2006)4288-4295, Ohki et al., Composites: Part A 35 (2004) 1065-1073. Howeverthe shape memory effect of these composites is also thermally induced,which may restrict their use in medical applications.

Biodegradable medical devices, which have shape-memory effect induced byphysiological conditions at temperature of 37° C., are described in U.SPatent application 20090149856.

Some objects of the present invention are to produce composites ordevices with an adequate mechanical properties and whose shapetransformation at physiological conditions can be controlled to obtainrapid and increased degree of the shape transformation. This may improvee.g. an initial and short term self-locking and fixation strength of themedical devices.

SUMMARY

The present invention provides a method to control the speed and degreeof the change of the shape of a deformed biodegradable polymer compositematerial or device for surgical applications, and a material or devicewhich has in physiological conditions, without additional externalstimulus, an ability to undergo a controlled dimensional change with acontrolled rate and extent, being at the same time able to exert forceson the healing tissues for a certain time. Controlled dimensional changemay be substantially immediate after exposure of the composite materialor device in physiological conditions.

According to a first aspect of the present invention there is provided abiodegradable composite material or a device which include at least onebiodegradable polymer matrix material and at least one filler component.A composite material or device has an initial shape and at least oneevolved shape. The evolved shape is different from the initial shape andthe initial shape is adapted to change towards the evolved shape.Evolved shape is recovered under external stimulus given byphysiological conditions. In the present invention filler blendingadvantageously accelerates and/or amplifies the transformation from theinitial shape towards the evolved shape in the physiological conditions.

According to an embodiment of the invention a filler component may behydrophilic enhancing water absorption. Due to the hydrophilic nature ofa filler a water uptake of the composite may also be increased. Fillercomponent may also have buffering capacity which will neutralize theacidic degradation products thus further enhancing the materialbiocompatibility. Filler component may also enhance visibility forexample during surgical operation or imagining.

According to an advantageous embodiment of the invention, polymer matrixconsists of biodegradable polymer, copolymer and/or polymer alloymatrix.

According to an advantageous embodiment of the invention, the initialshape is programmed to adapt towards a predetermined tension level andthe device is capable of restoring this predetermined tension level bystress generation or relaxation.

According to an embodiment of the invention, the amount of fillercomponent is 0.5-50 or more weight-%, preferably 5-15 weight-% and mostpreferably 5-10 weight-%.

According to a further aspect of the invention there is provided amethod to control the speed and degree of the change of the shape of abiodegradable polymer composite material or device. The methodcomprises: selecting a biodegradable polymer matrix material, selectinga filler component, selecting the relative amount of the fillercomponent in the mixture of the biodegradable polymer matrix materialand the filler component, mixing the biodegradable polymer matrixmaterial and the filler component in said relative amount byconventional melt processing to form a composite and programming of aninitial shape in a deformation process of the said composite.

According to an embodiment of the invention, the deformation processcomprises orientation of the composite using predetermined draw ratiobetween 1.5-10, preferably between 3-5.

DESCRIPTION OF THE DRAWINGS

In the following, the invention will be discussed with reference toaccompanying figures, where

FIG. 1 shows a schematic figure of a change of a shape of a compositematerial or device having a shape transformation capability,

FIG. 2 shows a schematic figure of an internal structure of a compositematerial or device after conventional melt processing having anon-oriented (non-programmed), original structure (2 A) and after solidstate deformation process having an orientation programmed, initialstructure (2 B),

FIG. 3 is a scanning electron microscope (SEM) figure of an internalstructure of an orientation programmed composite P(L/D)LA 50L/50D/β-TCP(10 wt-%) according to an example embodiment of the present invention,

FIG. 4 is a SEM figure of an internal structure of an orientationprogrammed P(L/D)LA 50L/50D,

FIG. 5A-B shows diagrams on the shape transformation of a pure copolymer(P(L/D)LA 50L/50D) and composites of P(L/DL)LA 50/50 withβ-tricalciumphosphate in simulating physiological conditions (in vitro),

FIG. 6 shows a diagram on the shape transformation of pure copolymerPLGA 85/15 and composites of PLGA 85/15 with β-tricalciumphosphate insimulating physiological conditions (in vitro),

FIG. 7 shows a diagram on the weight change of pure copolymer PLGA 85/15and composites of PLGA 85/15 with β-tricalciumphosphate in simulatingphysiological conditions, in vitro, due to the water absorption.

DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS

The present invention describes the ability of a composite material ordevice to change from initial shape towards the evolved shape (which isreferred also as shape transformation or shape-memory effect hereinafter) in certain controlled and predetermined speed and to provide apredetermined stress and/or strain in tissue conditions which furthergenerate substantially immediate self-locking and auto-compression ofthe device, such as nails, on the healing tissues, for example in thefracture fixation. In the present invention the combination ofshape-memory effect (shape transformation) and stress generation andrelaxation is designated as mechanically active shape-memory.

The present invention relates to a biocompatible, at least partiallybiodegradable composite material or medical device which is made of atleast one biodegradable matrix material, which biodegradable matrix maybe a synthetic or natural based or fully or partially degradable. Atleast one biodegradable matrix material may be selected from amongpolymers like homopolymers or copolymers. A polymeric matrix materialmay be an alloy of two or more polymers. In this application polymeralloy is referred also as a polymer blend. Biodegradable matrix materialmay also have a composition and/or structure which has shape-memorycapability or potential to be programmed to have shape-memory.

The biodegradable polymeric materials may be selected, for example, fromamong the following materials: polyglycolide (PGA), copolymers ofglycolide, polylactides, copolymers of polylactide, unsymmetrically3,6-substituted poly-1,4-dioxane-2,5 diones, poly-β-hydroxybutyrate(PHBA), PHBA/β-hydroxyvalerate copolymers (PHBA/HVA),poly-β-hydroxypropionate (PHPA), poly-p-dioxanone (PDS),poly-δ-valerolactone, poly-ε-caprolactone, methylmethacrylate-N-vinylpyrrolidine copolymers, polyesteramides, polyesters of oxalic acid,polydihydropyrans, polyalkyl-2-cyanoacrylates, polyurethanes (PU),polyvinylalcohol (PVA), polypeptides, poly-β-malic acid (PMLA),poly-β-alkanoic acids, polyethyleneoxide (PEO) and chitine polymers.Copolymers of glycolide comprise, for example, glycolide/L-lactidecopolymers (PGA/PLLA) and glycolide/trimethylene carbonate copolymers(PGA/TMC). Polylactides comprise, for example, poly-L-lactide (PLLA),poly-D-lactide (PDLA) and poly-DL-lactide (PDLLA). Copolymers ofpolylactide comprise, for example, L-lactide/DL-lactide copolymers,L-lactide/D-lactide copolymers, lactide/tetramethylglycolide copolymers,lactide/trimethylene carbonate copolymers, lactide/δ-valerolactonecopolymer, lactide/c caprolactone copolymer, polydepsipeptides(glycine-DL-lactide copolymer), polylactide/polyethylene oxidecopolymers, glycolide/L-lactide (PGA/PLLA)/polyethylene glycol (PEG)copolymers and polylactide/polyethylene glycol (PEG) copolymers.

According to an advantageous embodiment of the invention abiocompatible, biodegradable composite material or medical deviceconsist of at least one polymeric matrix component, and at least onedistinct constituent material or phase, on a scale larger than atomic.The matrix of a composite is preferably polymeric. Polymeric matrixenables the formation of oriented chain structure during orientationprogramming which further enables the mechanically active shape-memorybehaviour of the composite material or device in the physiologicalconditions. Physiological condition means in this context an aqueousenvironment and temperature at the range of 35° C. to 42° C. In vitrostudies are performed to simulate the physiological conditions.

A constituent phase may be a filler component, which may be at least oneof the following: an organic material, a inorganic material, a syntheticmaterial, a natural based material or any mixture of these. Theconstituent phase may contain only one type of filler component materialor several types of component materials. The filler component may or maynot have medical function or other effects to facilitate tissue healingand/or regeneration.

Several prior art patents describe, that oriented bioabsorbablematerials and implants (devices) containing powder-like ceramicmaterials (filler component) can be manufactured by solid statedeformation (like drawing) of bioabsorbable (biodegradable) polymerscontaining particles of a ceramic material, like calciumphosphate,hydroxyapatite, fluoroapatite or tricalciumphosphate, see e.g. U.S. Pat.Nos. 4,898,186, 4,968,317 and 6,228,111 B1. However, prior art does notteach that the filler component could be used to control and change thespeed and degree of the change of the shape of a biodegradable polymercomposite material or device.

The filler component preferably does not form essential chemical bondswith surrounding polymer matrix material. Thus between the polymermatrix and filler component there are preferably no strong interfacialprimary bonds such as covalent or ionic bonds. When the filler andmatrix component of the composite material are separate from each other,small cavities and/or voids are typically formed into the polymer matrixaround filler component, during the further orientation programmingprocess (solid state deformation). Thus the composite material or devicemay have a structure which consists within polymer matrix a fillercomponent and preferably small cavities around the filler component. Inaddition to the cavities, different orientation ratio may be formed inthe vicinity of the filler component, such as filler particles,comparing to that of in the polymeric regions lacking the particles.Small cavities may be beneficial in increasing a water absorption, whichmay further enhance a shape transformation rate of the compositematerial or device. A shape transformation rate is designated herein asa speed and/or a degree of a change of a shape of a composite materialor device.

Filler component may have different shapes such as 1) irregular,ellipsoidal, polyhedral, or spherical particle, with no long dimensions,2) fibre, with one long dimension, and 3) platelet or lamina, with twolong dimensions. Filler component may be also preferably at leastpartially rigid so that component is at least not in high extentdeformed during manufacturing. Partially rigid component may interferethe composite orientation programming process (solid state deformation)and generate an heterogeneously oriented polymer matrix, where thepolymer chains may have additional orientation in the vicinity of thefiller component. Heterogeneously oriented structure may lead to anenhanced shape transformation rate of a composite material or a device.

Filler component dimensions such as particle size and particle sizedistribution can be varied to tailor the composite structure and thusadjust the effect of filler component to shape-memory properties.Particle size and particle size distribution may affect on the size ofthe voids and/or cavities around the fillers particles as well as theorientation heterogeneity around the particles and thus either increaseor decrease the degree of shape transformation and/or shapetransformation speed towards the evolved shape.

Filler component may have a hydrophilic nature. When the hydrophiliccomponent is used as a filler material the water absorption of acomposite or a device may be increased. Increased water uptake mayfurther plasticize the polymeric structure of the composite and furtherenable deorientation of the polymer structure in physiologicalconditions. Deorientation means in this context relaxation of theoriented polymer chains. When the deorientation occurs polymer chains atleast partially contract towards the non-orientated state. At thebeginning of the deorientation there is no or at least no essentialdegradation of the molecular chains (chain scission). Thus devices andcomposites which have at least partially hydrophilic nature may haveenhanced shape transformation rate.

The composite material or device may also contain one or morebiologically active molecules or additives, such as chemotherapeuticagent, anti-inflammatory agent, antibiotic or other drugs, growthfactors, anticoagulants etc. Such composite material or device areadvantageous in clinical use, because they will further facilitatetissue healing and/or tissue generation or regeneration. These activemolecules or additives may or may not enhance the shape transformationrate.

A composite material or device may be manufactured using blending andconventional melt processing techniques like extrusion, injectionmoulding, compression moulding etc, to form a non-programmed originalshape. After conventional melt processing a composite material or devicecan be further processed (programmed), for example by means of solidstate deformation process (orientation programming). This deformationprocess creates the mechanically active shape-memory capability andproperties like maximum shape transformation capability and force thematerial is able to produce in tissue conditions of the composite ordevice. Deformation process is designated as programming or orientationprogramming. A shape of the composite material or device which is formedduring programming is designated as a programmed or an initial shape.

In the deformation process, the composite material or device of theoriginal shape is loaded with predetermined tension. The level of thepredetermined tension may depend e.g. on the initial geometry of thesample, programming/deformation temperature, deformation speed, coolingspeed and deformation ratio. The deformation ratio may also affect thedegree of dimensional change and stress generation and relaxation of thecomposite material or medical device.

The composite material or medical device may be manufactured andprogrammed so that it has the controlled and predetermined speed tochange towards the evolved shape after activation in the physiologicalconditions. When the polymeric phase of the composite material or deviceis deformed or programmed through solid state deformation processes,such as die-drawing, oriented polymer chain structure is created(programmed, initial shape). When the programming is done at temperatureabove polymer's glass transition temperature (T_(g)) but below themelting temperature (T_(m)), if any, of the polymer and quickly cooledto a temperature below T_(g), the deformed shape, also called programmedor initial shape, becomes frozen or fixed. This initial shape is thusadapted and may have an ability to change towards the evolved shape.

When the external stimulus for shape transformation is given byphysiological conditions or conditions simulating the physiologicalconditions there may occur relaxation/deorientation of the oriented andstressed polymer chains of the initial shape. Physiological conditionsmeans aqueous environment and temperature at the range 35° C. to 42° C.Thus after activation polymer chains tend to contract towards thenon-oriented (non-programmed) state, evolved shape, which ultimately isthe shape before programming. Although the composite material or deviceis programmed to change towards the evolved shape it does notnecessarily reach the evolved shape nor the original non-programmedshape.

The shape transformation of the composite device may be determined bymeasuring the dimensions, such as a diameter and length, of the deviceof initial shape and changed shape. Dimensions of the changed shape maybe measured as a function of time.

The degree and/or speed of the dimensional change and thus shapetransformation rate of a composite material or device may bepredetermined in more controlled way by changing the polymer matrixcomposition and preferably changing the composition of a compositematerial by adding an particular amount of filler component. Thus thefiller component may be adapted to accelerate and/or amplify and thus tocontrol the degree and/or speed of the shape transformation of thecomposite material or device. According to the invention, an addition ofa filler component may generate more rapid and increased degree of shapetransformation which is advantageous for example for initial and shortterm self-locking and fixation strength of medical devices made of thesecomposite materials. In this context initial means substantiallyimmediate and occurring within a time period of hours and short termdesignates time period from days to months. The amount of fillercomponent is at maximum 50 weight-% or more and at minimum 0.5 weight-%.However, as the person skilled in the art understands, there should beenough polymer matrix, which could form an oriented polymeric structure.The potential shape transformation (at maximum) of the compositematerial or device, which takes place during the change from initialshape towards the evolved shape depends on the orientation programmingof the composite material. Some examples are given in table below.

TABLE 1 Potential shape transformation. Non- Orientation programmedprogrammed Potential shape rod (diameter Draw- rod (diametertransformation (%) D2, mm) ratio D1, mm) (D2 − D1)/D1 * 100% 16 10 5.1216.2 16 8 5.7 182.8 16 6 6.5 145 16 4 8 100 16 2 11.3 41.4 6 10 1.9216.2 6 8 2.1 182.8 6 6 2.5 145 6 4 3 100 6 2 4.2 41.4

The mechanically active shape-memory effect and shape transformation ofa composite or device may be based on the deorientation of the oriented,extra oriented (more extended polymer chains in the vicinity of thefiller component, such as particles) and stressed polymer chains.However the mechanically active shape-memory potential may also bedependent on the molecular structure, molecular weight and morphology ofthe polymer such as amorphous, crystalline or semicrystalline structure.

During orientation programming (solid state deformation process) of acomposite material or device at least partially additional orientedstructure may be formed. This additional oriented structure means inthis context that at least some of the polymer chains, which areoriented during the process, are more oriented (more extended) and havehigher orientation ratio than the rest of the polymer chains. This maybe due to the filler component like particles which interfere with thedeforming process.

EXAMPLE 1

P(L/D)LA 50L/50D and β-TCP are melt mixed in twin screw extruder andextruded into round rods having the diameter of 3 mm. The extrudertemperatures are between 50° C. and 280° C. The 3 mm rods are then diedrawn into 1.5 mm rods with drawing temperatures between 60° C. and 120°C. and subsequently cooled down to room temperature. The draw ratio ofthe programmed rods is then 4. Similar rods are made of pure P(L/D)LA50L/50D. Internal structures of these materials are presented in FIG. 3and FIG. 4. In simulated body conditions, in vitro, the programmedP(L/D)LA 50L/50D-βTCP-composites have remarkably shorter latency timebefore the shape transformation starts, higher short term shapetransformation and higher shape transformation speed than the pureP(L/D)LA 50L/50D copolymer processed similar way, as presented in FIGS.5 A and 5 B.

EXAMPLE 2

PLGA 85L/15G and β-TCP are melt mixed in twin screw extruder andextruded into round rods having the diameter of 5.5 mm. The extrudertemperatures are between 50° C. and 300° C. The 5.5 mm rods are then diedrawn into 2.7 mm grooved surfaced rods with drawing temperaturesbetween 60° C. and 140° C. and subsequently cooled down to roomtemperature. The draw ratio of the programmed rods is then 4.1. Insimulated body conditions, in vitro, the programmed PLGA85L/15G-βTCP-composites have remarkably shorter latency time before theshape transformation starts, higher short term shape transformation andshape transformation speed than the pure PLGA 85L/15G copolymer, aspresented in FIG. 6. Shape transformation ratio is according to theβ-TCP concentration (0, 10, 15 and 20 wt-%) of the composite; the higherparticle concentration the higher shape transformation ratio in thesimulated body conditions.

FIG. 1. shows a schematic figure of a shape transformation and a changeof a shape of a composite material or device when it has a shape-memorycapability. As presented in FIG. 1. the composite material or device ofpresent invention have an ability to change from programmed initialshape 1 towards the evolved shape 2. The dimensions are presented aslength L1 and diameter D1 for the programmed initial shape and length L2and diameter D2 for evolved shape. The composite material or medicaldevice has a programmed initial shape and at least one evolved shape.The initial programmed shape is adapted to change towards the evolvedshape when the composite material or medical device is activated inphysiological conditions or in conditions simulating the physiologicalconditions. The degree and/or speed of the shape transformation of thecomposite material or device may be adjusted by controlling the amountand type of the filler component.

FIG. 2. shows a principle internal view of a composite material ordevice after conventional melt processing having a non-oriented,original structure (2 A) and after orientation programming process(solid state deformation) having an oriented (programmed), initialstructure (2 B). Partially rigid components (like spheres in a figure)may interfere the composite solid state deformation process and generatean heterogeneously oriented polymer matrix, where the polymer chains mayhave additional orientation and higher orientation rate in the vicinityof the filler component (shown by darker line around the spheres).Heterogeneous orientation may further have influence on thetransformation rate profile of the composite material or device.

According to an example embodiment of the present invention an initialinternal structure of an orientation programmed composite, P(L/D)LA50L/50D/β-TCP (10 wt-%), with draw ratio 4 is shown in FIG. 3. Internalstructure of an orientation programmed polymer, P(L/D)LA 50L/50D withdraw ratio 4, is shown in FIG. 4.

FIG. 5. A and B present the acceleration and amplification of the shapetransformation rate in a well controlled manner by adding fillerparticles. The tests were carried out by immersing the samples inphosphate buffered saline at 37° C. and periodically measuring thedimensions manually using a slide gauge. In vitro time (days) ispresented in x-axis and shape transformation (%) in y-axis. Radialexpansion (change in diameter upwards) and longitudinal contraction(change in length downwards) of y-axis. The dimensional change whichtakes place during the shape transformation in physiological conditions,may be remarkably increased when the material is blended with particlefiller material. For example the diameter of the composites which has 10weight-% filler may be increased by 10% in 2 days, whereas the lengthmay be decreased by 18%, as presented in FIG. 5 B. Pure copolymerP(L/D)LA 50L/50D has less shape transformation capability and normally24 to 48 h time lag of shape transformation to occur at the beginning ofexposure to physiological conditions. It is obvious that fillercomponent and thus particle blending change the transformation rateprofile of composites. The time lag diminishes and shape transformationrate can be adjusted to desired and predetermined level by varying theparticle content. Increased shape transformation may be achieved alsowith relatively small particle content e.g. such as from 5 to 10weight-%.

FIG. 6. shows a diagram of a shape transformation of a pure copolymerPLGA 85L/15G and composites of PLGA 85L/15G with β-tricalciumphosphatein physiological conditions until 84 days. The test is carried out byimmersing the samples in phosphate buffered saline at 37° C. andperiodically measuring the dimensions manually using a slide gauge. Invitro time (days) is presented in x-axis and shape transformation (%) iny-axis. Radial expansion (change in diameter upwards) and longitudinalcontraction (change in length downwards) of y-axis. The dimensionalchange, both diameter and length, is rapid at the beginning of thehydrolysis. For example by 7 days all the materials have reached most ofthe transformation of the sample length, which thereafter continues slowdecrease until 84 days. The shape transformation rate of the compositematerials or devices may thus be enhanced at the beginning of theimmersion.

FIG. 7. shows a diagram on the weight change of pure copolymer PLGA85L/15G and composites of PLGA 85L/15G with β-tricalciumphosphateparticles in physiological conditions due to the water absorption. Thetest is carried out by immersing the samples in phosphate bufferedsaline at 37° C. and periodically weighing the samples. In vitro time(days) are presented in x-axis and wet mass increase (%) in y-axis. Asseen the hydrophilic filler particles increase the wet mass of thecomposites during the whole period, 84 days. Wet mass of a pure polymeris increased from 0.8 to 1.2 weight-% during 84 day follow up timewhereas the wet mass of composite having 20 weight-% particles isincreased from 1.3 to 3.6 weight-%. Thus water absorption of compositematerials or devices may be increased by adding a hydrophilic fillercomponent into the polymer matrix.

The embodiments described above are only exemplary embodiments of theinvention and a person skilled in the art recognizes readily that theymay be combined in various ways to generate further embodiments withoutdeviating from the basic underlying invention.

The invention claimed is:
 1. A biodegradable composite material ordevice having an orientation programmed initial shape having orientationdraw ratio between 2 and 10, and at least one evolved shape beingdifferent from the initial shape, wherein the orientation programmedinitial shape adapts toward a predetermined tension level and is capableof restoring the predetermined tension level by stress generation orrelaxation, and wherein the material or device comprises: abiodegradable polymer matrix material consisting of L-lactide/D-lactidecopolymer or L-lactide/glycolide copolymer and a filler componentconsisting of β-tricalciumphosphate in an amount between 5 and 15 weight-%, and wherein the composite material or device has a structureconsisting of polymer matrix having a uniaxial heterogeneous orientationand cavities around filler component particles, wherein the structureaccelerates or amplifies transformation from the initial shape towardsthe evolved shape when an external stimulus for transformation is givenby physiological conditions comprising an aqueous environment and atemperature of 35° C. to 42° C. thus enabling a shortened latency timeof the transformation or amplified transformation of dimensions of thematerial or device as compared to a material or device without thefiller component.
 2. The composite material or device according to claim1, wherein the filler component does not form essential bonds withsurrounding biodegradable polymer matrix material.
 3. The composite ordevice according to claim 1, wherein said filler component has bufferingproperty.
 4. The composite material or device according to claim 1,wherein said filler component enhances visibility.